Neonates on extracorporeal life support (ECLS) have the highest rate of protein catabolism ever reported. Interventions designed to limit this process remain sparsely investigated despite the association between protein loss and increased morbidity and mortality in surgical patients. This proposal seeks to test the hypothesis that the intravenous administration of insulin will improve the extreme protein catabolism in neonates on ECLS. Such an investigation is significant as ECLS is a lifesaving surgical therapy that has been utilized in over 16,000 babies with cardiac and respiratory failure. However, morbidity remains high, and the attendant mortality has stayed constant at 15-20 % over the past decade. [unreadable] A pilot study of a prospective, randomized, crossover trial is proposed using neonates on ECLS as a model of neonatal critical illness and employing validated stable isotope tracer techniques to quantify protein metabolism. The protocol is designed to determine if the application of a hyperinsulinemic euglycemic clamp in parenterally fed neonates on ECLS will result in an improvement in protein balance. Secondly, the study aims to elucidate the mechanisms of the alteration in protein balance through assessment of both whole body and hepatic insulin sensitivity. [unreadable] This fundamental metabolic investigation has the potential to improve the management of neonates requiring ECLS and is important in defining how net protein balance may be optimized in a wide range of critically ill surgical neonates. [unreadable] [unreadable]